Streptococcus pneumoniae as cause of acute otitis media (AOM) in Slovak children in the pneumococcal conjugate vaccine era (2008–2019)

AimLittle data is available on pneumococcal serotypes and their antimicrobial resistance in the pneumococcal conjugate vaccination era in young children with acute otitis media (AOM). Here such data is provided from Slovakia, a country with sequential introduction and parallel-use of the three commercially available pneumococcal conjugate vaccines (PCVs; PCV7; PCV13; PCV10).MethodsThis observational study takes advantage of the fact that tympanocentesis is the standard of care in children with AOM in Slovakia. Over the 12 year observation period, participating pediatric ENT specialists sent samples taken during tympanocentesis from children with AOM to their local MEDIRIX laboratories for identification of bacteria. Pneumcoccal isolates were serotyped and tested for antimicrobial resistance. Incidence data could be calculated from 1 region.ResultsStudy participation and completeness of typing increased over time. Based on testing of 1,131 isolates over 12 years, PCV7-serotypes rapidly waned after PCV7 introduction in 2009 and had virtually disappeared in 2014. The maximum fraction of PCV10-only isolates (1, 5, 7F) was 2.7 % (2009) whereas the additional 3 PCV-serotypes (3, 6A, 19A) in PCV13 represented the largest proportion of pneumococcal AOM cases as of 2010. This finding remained unchanged during the period of highest PCV10-market share (2012–2017) and even until the end of the observation period (2019). The fraction of untypeable pneumococci (<6 %) and non-PCV13-serotypes (16–34 %) increased 2012–2017, but decreased again thereafter. Serotype 19A evolved as the most relevant (multidrug-) resistant pneumococcal serotype, again particularly during the time with high sales of PCV10 (2012–2017). Incidence data from the Bratislava region document a huge impact of PCV use (77 % vaccine uptake: mainly PCV13) on AOM in children < 6 years. Serotypes 19A and 3 remain the only relevant pneumococcal serotypes in young Slovakian children with AOM.ConclusionsAs AOM is one of the most common bacterial infections in children < 6 years, the observed benefits of PCVs in reducing vaccine serotypes have been tremendous. With sequential / parallel-use of PCVs, serotypes 3 and (MDR-) 19A today make the largest proportion (about 2/3) of pneumococcal AOM in Slovakia. This data will help to further guide the choice of pneumococcal conjugate vaccines for pediatricians and parents.     

Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme

BackgroundIn Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007–2011) to PCV13 (2011–2015) and to PCV10 (2015–2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance.Materials/methodsTwo infant populations aged 6–30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed.ResultsCulture-based (DCC: 462/760; 60.8% – AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% – AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 10⁶ copies/µl (95%CI = 3.9–9.2 × 10⁶, median = 3.5 × 10⁵); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively.ConclusionFour years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.     

A β-mannan trisaccharide conjugate vaccine aids clearance of Candida albicans in immunocompromised rabbits

A β-(1→2)-linked mannose trisaccharide epitope that is the optimal inhibitor of two protective monoclonal antibodies specific for the Candida albicans cell wall phosphomannan was used to create a synthetic conjugate vaccine. Two injections of the trisaccharide-tetanus toxoid conjugate administered with alum induced a robust secondary antibody response in rabbits with trisaccharide specific IgG ELISA titers in excess of 1:100,000. Fluorescent labeling studies demonstrated these antibodies (i) recognized the cell wall β-mannan of C. albicans on hyphae and budding cells and (ii) C. albicans incubated with immune sera bound complement factor C3. The synthetic conjugate vaccine but not the carrier protein, tetanus toxoid reduced Candida load in vaccinated rabbits subsequently rendered leukocytopenic by injection of cyclophosphamide and then challenged with live C. albicans. These data support the contention that antibody mediated immunity plays a role in combating C. albicans infections and suggests that a surprisingly simple, readily accessible synthetic conjugate vaccine may have therapeutic potential.     

Use of a conjugate polysaccharide vaccine in the prevention of invasive staphylococcal disease: is an additional vaccine needed or possible?

Staphylococcus aureus is a ubiquitous bacterial species that causes serious disease in certain settings. S. aureus disease is difficult to treat, and antibiotic-resistant strains have become common. A vaccine to protect against infection would therefore be beneficial. However, the virulence of S. aureus is determined by a number of different factors, which makes design of a widely effective vaccine difficult. Here, various bacterial virulence factors and attempts to develop vaccines based on these factors are briefly reviewed. In particular, the success of a Phase 3 clinical study of a vaccine directed at capsular polysaccharides types 5 and 8 is discussed.     

Serogroup A meningococcal conjugate (PsA-TT) vaccine coverage and measles vaccine coverage in Burkina Faso—Implications for introduction of PsA-TT into the Expanded Programme on Immunization

BackgroundA new serogroup A meningococcal conjugate vaccine (PsA-TT, MenAfriVac™) has been developed to combat devastating serogroup A Neisseria meningitis (MenA) epidemics in Africa. A mass immunization campaign targeting 1–29 year olds was conducted in Burkina Faso in December 2010. Protection of subsequent infant cohorts will be necessary through either introduction of PsA-TT into the routine Expanded Programme on Immunization (EPI) or periodic repeat mass vaccination campaigns.ObjectivesTo inform future immunization policy for PsA-TT vaccination of infants through a comparison of PsA-TT campaign vaccination coverage and routine measles-containing vaccine (MCV) coverage in Burkina Faso.MethodsA national survey was conducted in Burkina Faso during December 17–27, 2011 using stratified cluster sampling to assess PsA-TT vaccine coverage achieved by the 2010 nationwide immunization campaign among 2–30 year olds and routine MCV coverage among 12–23 month olds. Coverage estimates and 95% Confidence Intervals (CI) were calculated, reasons for non-vaccination and methods of campaign communication were described, and a multivariable analysis for factors associated with vaccination was conducted.ResultsNational overall PsA-TT campaign coverage was 95.9% (95% CI: 95.0–96.7) with coverage greater than 90% all 13 regions of Burkina Faso. National overall routine MCV coverage was 92.5% (95% CI: 90.5–94.1), but ranged from 75.3% to 95.3% by region. The primary predictor for PsA-TT vaccination among all age groups was a head of household informed of the campaign. PsA-TT vaccination was more likely in residents of rural settings, whereas MCV vaccination was more likely in residents of urban settings.ConclusionOverall national vaccination rates in Burkina Faso were similar for PsA-TT and MCV vaccine. The regions with MCV coverage below targets may be at risk for sub-optimal vaccination coverage if PsA-TT is introduced in EPI. These results highlight the need for assessments of routine vaccination coverage to guide PsA-TT immunization policy in meningitis belt countries.     

Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.     

Persistence of bactericidal antibodies 4 years after a booster dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D)

One dose of quadrivalent meningococcal conjugate vaccine (MenACWY) was first recommended for US adolescents (ages 11–12?years) in 2005 to protect against invasive meningococcal disease (IMD). In 2010, after evidence emerged about waning protection within 5?years after MenACWY vaccination, the US Advisory Committee on Immunization Practices (ACIP) recommended a MenACWY booster at age 16?years. We used a serum bactericidal assay with human complement (hSBA) to evaluate antibody persistence after a MenACWY-D booster in a sample of 110 participants who received the booster 4?years earlier in a phase 2 study. High proportions (89.9–98.2%) of participants maintained hSBA titers (≥1:4) associated with protection against IMD; a majority (81.7–97.2%) also had hSBA titers ≥1:8, a more conservative threshold. These findings support ACIP recommendations regarding MenACWY booster vaccination, which are aimed at protecting adolescents and young adults throughout the period in which they are at increased risk of IMD.     

Could a single dose of pneumococcal conjugate vaccine in children be effective? Modeling the optimal age of vaccination

Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.     

Acute otitis media in the era of effective pneumococcal conjugate vaccine: will new pathogens emerge?

The immunogenicity of pneumococcal conjugate vaccine (PCV) in young infants and its serotype-specific efficacy in otitis media (OM) results in a modest reduction in total episodes of OM and a more substantial reduction in disease due to the most frequent pneumococcal serotypes. Since PCV will only prevent disease due to the most common serotypes, concerns about potential changes in the microbiology of OM have emerged. Insight into potential changes can be obtained from reviewing middle ear and nasopharyngeal isolates from studies of antimicrobial prophylaxis and bacterial polysaccharide immune globulin for prevention of OM and PCV for prevention of invasive pneumococcal disease, respectively. In children receiving PCV, a shift in serotypes of SP colonizing the nasopharynx has been observed. Since non-vaccine serotypes are already present in the community as the etiology of acute purulent OM, it is predictable that these non-vaccine serotypes will become more common especially in children less than two years of age.     

The effect of 23-valent pneumococcal polysaccharide vaccine on immunological priming induced by 7-valent conjugate vaccine in asplenic subjects with β-thalassemia

The effect of the 23-valent pneumococcal polysaccharide vaccine (PPV) on the 7-valent conjugate (PCV) vaccine-induced priming was evaluated in 35 splenectomised β-thalassemics [median (range) age: 30 (12–41) years] vaccinated with either PCV/PPV or two PCVs 1 month apart, followed by a PPV booster 12 months later. 28/35 had already received 1–3 PPVs in the past. Different schedules induced similar anamnestic responses; however priming for 3/5 serotypes induced by one or two PCVs, was inferior in subjects who had received ≥2 PPVs in the past when compared with 23 aged-matched PPV-naïve β-thalassemics. One PPV following PCV does not affect PCV priming; multiple PPVs induce hyporesponsiveness for some serotypes in splenectomised subjects with β-thalassemia.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18–49 years of age,naive to 23-valent pneumococcal polysaccharide vaccine

BackgroundBased on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60–64 years of age have been published. The same study also included a cohort of adults aged 18–49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18–49 years of age compared with adults 60–64 years of age for whom PCV13 is approved.MethodsAdults naive to PPSV23 were grouped by age into 2 cohorts: 18–49 years (n = 899; further stratified by age into 3 subgroups 18–29, 30–39, and 40–49 years) and 60–64 years (n = 417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated.ResultsIn adults aged 18–49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60–64 years. Immune responses were highest in the youngest age subgroup (18–29 years). Local reactions and systemic events were more common in adults 18–49 years compared with 60–64 years and were self-limited.ConclusionImmune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.     

Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010–2018

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger.As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010–2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010–2012) and after (2016–2018) PCV13 introduction.During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010–12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016–18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years.VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age

BackgroundPneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).Methods691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination.ResultsSafety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23).ConclusionsPCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines.Study identification: V114-002.CLINICALTRIALS.GOV identifier: NCT01513551.© 2018 Merck & Co., Inc.     

Public health and economic impact of 13-valent pneumococcal conjugate vaccine in US adults aged ≥50 years

Background

A 13-valent pneumococcal conjugate vaccine (PCV13) was recently developed for use in older adults, and may be effective not only against invasive pneumococcal disease (IPD) but also nonbacteremic pneumococcal pneumonia. The potential public health and economic impact of PCV13 in this population is unknown.

Methods

A microsimulation model depicting risk and costs of IPD and all-cause nonbacteremic pneumonia (NBP) in US adults aged ≥50 years (n = 96.1 million), as well as expected impact of vaccination, was developed. Effectiveness of PPSV23 was based on published literature, and for all-cause NBP, was zero; effectiveness of PCV13 was based on PCV7 data in children, and for all-cause NBP, was varied across a reasonable range. Lifetime outcomes and costs were projected assuming: (1) use of PCV13 in all subjects at model entry, with and without periodic revaccination; and (2) use of PPSV23 per current ACIP recommendations.

Results

Use of PCV13 in all subjects at model entry without revaccination – in lieu of PPSV23 use per recommendations – reduced cases of IPD by 15,000 (95% CI 9000–21,000); cases of NBP by 1.2 million (0.9–1.5); total healthcare costs by $3.5 billion (1.9–5.2); and total societal costs by $7.4 billion (5.3–9.8). Use of PCV13 with revaccination every 5–10 years resulted in fewest cases of disease and lowest total costs. Findings were largely unchanged in sensitivity analyses.

Conclusions

Assuming that the effectiveness of PCV13 in adults is comparable to that observed for PCV7 in children and under reasonable assumptions regarding the underlying risks and costs of IPD and NBP, model projections suggest that routine use of PCV13 – in lieu of PPSV23 – would result in a greater reduction in the overall burden of pneumococcal disease in older US adults.     

Dose-ranging study of a single injection of pneumococcal conjugate vaccine (1 ×, 2 ×, or 4 ×) in healthy subjects aged 70 years or older

Healthy adults aged ≥70 years (N = 443) with no history of pneumococcal vaccination received 7- or 9-valent pneumococcal conjugate vaccine (PCV7 or PCV9) at 1× (PCV7 only), 2× (PCV7 + PCV9), or 4× (2× PCV7 + 2× PCV9) dosage in a randomised, open-label study evaluating pneumococcal protein conjugate vaccine (PnC). Controls received 23-valent pneumococcal polysaccharide vaccine (PPV). Both geometric mean concentration enzyme-linked immunosorbent assay and opsonophagocytic activity antibody titres assessed 1 month after vaccination were significantly increased over baseline titres for all PCV7 serotypes, with a trend toward a dose-dependent immune response. Local reactions for the 4× dose, but not the 2× dose, were statistically significantly higher than for the 1× dose. No treatment-related serious adverse events occurred.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine and an MF59-adjuvanted influenza vaccine after concomitant vaccination in ⩾60-year-old adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time.MethodsSubjects aged ⩾60 years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV) + 13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination.ResultsA total of 1149 subjects (Group 1, N = 373; Group 2, N = 394; Group 3, N = 382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred.ConclusionsConcomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles.(Clinical Trial Number – NCT02215863).     

Rapid identification of herd effects with the introduction of serogroup C meningococcal conjugate vaccine in Ontario,Canada, 2000–2006

In 2001, Canada's National Advisory Committee on Immunization endorsed a meningococcal serogroup C conjugate vaccine, which appears to provide durable serogroup-specific immunity while reducing nasopharyngeal carriage. With reference to direct and indirect effects on case occurrence, we sought to evaluate recent trends in the incidence of invasive meningococcal disease (IMD) in Ontario. Analyses included all IMD cases reported between 2000 and 2006 to the Ontario Central Public Health Laboratory. Poisson models incorporating terms for age, sex and seasonal oscillation identified a significant downward trend in disease occurrence, which was strongest in serogroup C cases and not evident when serogroup C strains were excluded from the analysis. Among age groups not targeted by the vaccine program serogroup C, IMD displayed a pattern of decreasing incidence that was not present in non-serogroup C disease. These apparent dramatic effects of conjugate C vaccine (both direct and indirect) may be important in the implementation and evaluation of vaccine policy in other jurisdictions.     

Immunogenicity and safety of measles-mumps-rubella-varicella (MMRV) vaccine followed by one dose of varicella vaccine in children aged 15 months–2 years or 2–6 years primed with measles-mumps-rubella (MMR) vaccine

In this open, randomized, comparative study (105908/NCT00353288), 458 age-stratified children (15 months–2 years and 2–6 years) previously primed with MMR received one dose of either a combined MMRV vaccine (Priorix-Tetra™, MMRV group) or concomitant MMR and varicella vaccines (Priorix™ and Varilrix™, MMR + V group), followed 42–56 days later by another dose of varicella vaccine (Varilrix™) in both groups. Post-vaccination measles, mumps and rubella seropositivity rates and antibody geometric mean titers (GMTs) were high (99.5% for anti-measles and 100% for anti-mumps and anti-rubella) in both vaccine groups. In the two age strata, varicella seroconversion rates were, post-dose 1: ≥97.6% (MMRV), ≥96.6% (MMR + V) and, post-dose 2: 100% in both groups. Post-dose 2, anti-varicella GMTs increased respectively 14.1- and 12.6-fold (MMRV), and 9.8- and 13.1-fold (MMR + V). Both vaccine regimens were well-tolerated. Post-dose 1, the incidence of any solicited local symptom during the 4-days follow-up was ≤28.2% (MMRV) and ≤19.8% (MMR + V) and the incidence of fever >39.5 °C (rectal temperature) within 15 days was ≤2.8% (MMRV) and ≤2.6% (MMR + V). This MMRV vaccine appears an immunogenic and safe substitute for a second dose of MMR vaccine in young children. The increase in anti-varicella antibodies observed after a second dose of varicella vaccine supports a two-dose schedule for varicella-containing vaccine.     

Impact of BRICS’ investment in vaccine development on the global vaccine market

Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.